894 resultados para Toxic Effects


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Up to now, in vivo studies on the toxic effects of microcystins (MCs) on the ultrastructures of fish liver have been very limited. The phytoplanktivorous silver carp was injected i.p. with extracted hepatotoxic microcystins (mainly MC-RR and -LR) at a dose of 1000 mu g MC-LReq. kg(-1) body weight, showing a time-dependent ultrastructural change in liver as well as significant increases in enzyme activity of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). We observed for the first time the occurrence of a large amount of activated secondary lysosomes, which might be an adaptive mechanism to eliminate or lessen cell damage caused by MCs through lysosome activation. Quantitative and qualitative determinations of MCs in the liver were conducted by HPLC and LC-MS2, respectively. MCs concentration in the liver reached the maximum (114.20 mu g g(-1) dry weight) after 3 h post-injection, and then rapidly dropped to 7.57 mu g g(-1) dry weight at 48 h, indicating a deputation of 99% accumulated MC-LReq. On the other hand, a decrease trend in glutathione (GSH) concentration was observed in the liver of silver carp while the activity of glutathione S-transferase (GST) increased significantly after injection. The high tolerance of silver carp to MCs might be due to the high basic GSH level in their liver, and/or an increased GSH synthesis. (C) 2007 Elsevier Inc. All rights reserved.

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The toxicity of hepatotoxic microcystins produced mainly by Microcystis aeruginosa in mammals and fishes was well studied in recent years. However, there were scarcely reports in toxic effects of microcystins on isolated hepatocytes of fishes, especially investigation of microcystin-induced apoptosis and/or necrosis in carp hepatocytes. In the present study, the isolated hepatocytes of common carp were exposed to various concentrations of microcystins (0.01, 0.1, 1, 10, 100, 1000 mu g L-1) for 2, 4, 8, 16 and 24 h, respectively, and cytotoxicity of microcystins in the toxin-treated cells was determined. Results of this study showed that cytotoxicity of microcystins on carp hepatocytes was time and dose-dependent, and the approximate LC50 of microcystins in carp hepatocytes was 169.2 mu g L-1. The morphological changes typical of apoptosis, such as blebbing of cell membrane, condensation and fragmentation of cell nucleus were observed in the hepatocytes exposed to microcystins (1, 10 and 100 mu g L-1) using fluorescence and differential interference contrast microscopy. Agarose gel electrophoresis of DNA demonstrated a typical apoptotic "ladder pattern" in microcystin-treated hepatocytes after 16 h of exposure. Results of the present study indicated that the form of cell death in microcystin-treated hepatocytes depend on the exposure dose of toxin. When lower concentration of microcystins (10 and 100 mu g L-1) was used for exposure, carp hepatocytes died in apoptosis while, when higher one used (1000 mu g L-1), they died in the form of necrosis. (C) 2006 Elsevier Inc. All rights reserved.

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The oligohaline cyanobacterium Aphanizomenon flos-aquae (L.) Ralfs (A. flos-aquae) has been reported in several countries to produce paralytic shellfish poisons (PSPs) or protracted toxic effects. In the past years, A. flos-aquae blooms have occurred annually in the eutrophic Lake Dianchi (300 km(2) in area, located in southwestern China). Material from natural blooms dominated by A. flosaquae was collected and lyophilized. Acute toxicity testing was performed by mouse bioassay using extracts from the lyophilized material. Clear symptoms of PSPs, intoxications were observed. To confirm the production of PSPs, a strain of A. flos-aquae (DC-1) was isolated and maintained in culture. Histopathological effects were studied by examining the organ damages using transmission electron microscopy (TEM). Slight hepatocytic damage with swollen mitochondria was found. The ultrastructural pulmonary lesions were characterized by distortied nuclei and indenting of karyotheca, together with degeneration and tumefaction of mitochondria and endoplasmic reticulum. Control animals injected with acetic acid did not exhibit histopathological damage in any organ. Toxic effects of cultured algal cells on enzymatic systems in the mouse were studied using sublethal doses of extracts. Significant glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) increases, together with decrease of the glutathione (GSH) level, were measured. These results indicated a potential role of PSPs intoxicating and metabolizing in the test animals. HPLC-FLD and LC/MS analysis of extracts from cultured material demonstrated the PSP toxins produced by A. flos-aquae bloom. To the best of our knowledge, this is the first study reporting chemically and toxicologically confirmed PSP toxins related to A. flosaquae in China. (c) 2005 Elsevier Inc. All rights reserved.

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Persistent bioaccumulative toxins (PBTs) are organic substances that are persistent, bioaccumulative and can cause severe toxic effects (e.g. potential oncogens, mutagenic, endocrine disrupters) to human health or environment which are the ones that need special attention. PBT chemicals could be released to the environment from several types of sources and are ubiquitous in environment. However, fast and efficiency monitoring and assessment methods to investigate PBTs in environment are still lacking. In this study, a cleaning-up procedure of analyzing PBTs in fuels combustion soot was developed and its performance was assessed through comparing the chromatograms of crude extracts with their cleaned extracts after the cleaning-up procedure. The results showed that polycyclic aromatic compounds (PACs) were the main components in fuel combustion soot and the clean-up procedure developed in this paper can be well used as the method of analyzing PBTs in fuels combustion soot.

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Microcystins are cyclic heptapeptide hepatoxins produced by many species of cyanobacteria. The toxic effects and mechanism of microcystins on animals have been well studied both in vivo and in vitro. It was also reported that microcystins had adverse effects on plants. However, to our knowledge, there is no information about the toxic effects and mechanism of microcystins on plant suspension cells. In this study, Arabidopsis thaliana suspension cells were exposed to a range dose of microcystin-RR. Lipid peroxidation, a main manifestation of oxidative damage, was studied and a time- and dose-dependent increase in malondiadehyde was observed. In contrast, glutathione (GSH) levels in the cells decreased after 48 h treatment with 1 and 5 mg/L of microcystin-RR. The activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after 48 h exposure to I and 5 mg/L of microcystin-RR, but glutathione S-transferase (GST) activity showed no difference compared with the control. These results clearly indicate that microcystin-RR is able to cause oxidative damage in A. thaliana suspension cells. Decrease of GSH content and increases of SOD and CAT activities reveal that the antioxidant system may play an important role in eliminating or alleviating the toxicity of microcystin-RR. The possible toxicity mechanism of microcystin-RR on the A. thaliana suspension cells is also discussed in this paper. (C) 2005 Elsevier Ltd. All rights reserved.

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Microcystins, one type of the cyanobacterial toxins, show a broad range of hazardous effects on other organisms. Most of the researches on the toxic effects of microcystins have involved in animals and higher plants. Little work, however, has been done on evaluating the mechanisms of microcystin toxicity on algae. In this study, the toxicological effects of microcystin-RR (MC-RR) on the cyanobacterium Synechococcus elongatus were investigated. For this purpose, six physio-biochemical parameters (cell optical density, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST)) were tested in algal cells when exposed to 100 mug(-1) microcystin-RR. The results showed that the growth of Synechococcus elongatus ( expressed as optical density) was significantly inhibited compared with the control. At the same time, the treated algae exhibited a pronounced increase in production of ROS and MDA after 6 days exposure to microcystin-RR. Signi. cant changes in GSH levels and GSH-Px, GSH activities were also detected in algal cells, with higher values being observed in the toxin treated algae after 6 days exposure. GST activities in the treated algae exhibited a decline after exposure and rapid augmentation on day 3, thereafter, they kept at a high level when compared to the control group. GSH contents and GSH-Px activities were also significantly raised in the toxin-treated algae cells from day 3, but they showed a sharp decrease on day 4, which was the onward of cell proliferation. These results suggested that oxidative stress manifested by elevated ROS levels and MDA contents might be responsible for the toxicity of microcystin to Synechococcus elongatus and the algal cells could improve their antioxidant ability through the enhancement of enzymatic and non-enzymatic preventive substances.

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为了探讨重金属对矮小拟丽突线虫(Acrobeloides nanus)的毒性作用,本文采用室内培养的方法,研究了不同浓度Cu、Zn、Pb、Cd对矮小拟丽突线虫死亡率、生长发育和繁殖的影响,并对线虫世代间的毒性效应进行了比较。结果表明:1)Cu、Zn、Pb、Cd对矮小拟丽突线虫24 h的半致死浓度LC50值分别为 0.80、71.20、12.94 和 1.42 mg • L-1,48 h 的半致死浓度LC50值分别为 0.71、35.08、2.65 和 0.32 mg • L-1。不同重金属离子对矮小拟丽突线虫产生的毒性具有一定的差异,24 h四种重金属离子对矮小拟丽突线虫的毒性大小依次为Cu > Cd > Pb > Zn,48 h毒性大小依次为Cd > Cu > Pb > Zn;2)与对照组相比,各暴露组当代(P0)和后代(F1)线虫平均体长均显著降低(P<0.05, P<0.01);随着暴露浓度的增加,当代(P0)和后代(F1)线虫平均体长呈逐渐降低的趋势。生物量比体长更能敏感地反应重金属对矮小拟丽突线虫生长发育的影响,可作为重金属污染的敏感检测指标;3)供试线虫的产卵数随着Cu、Zn、Pb、Cd暴露浓度的增加而降低;其中Cu对线虫产卵数的72h-EC50、EC20和EC10值分别为1.35、0.49 和 0.2mg • L-1,Zn的72h-EC20和EC10值分别为330.29 和 163.9 mg • L-1,Pb的72h-EC20、EC10分别为17.41、4.36 mg•L-1,而Cd对线虫产卵数的72h-EC50、EC20和EC10分别为4.47、0.91 和 0.53 mg • L-1。研究结果表明,重金属Cu、Zn、Pb、Cd暴露可显著抑制矮小拟丽突线虫的生长发育和繁殖;线虫体长、产卵数表现出明显的重金属浓度依赖性。

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Traditional Chinese medicines (TCMs), due to their long time clinic test and reliable therapeutic efficacy, are attracting increased global attention served as excellent pools of bioactive compounds for the discovery of new drugs. However, hundreds or even thousands of components are usually contained in traditional Chinese medicines and only a few compounds are responsible for the pharmaceutical and/or toxic effects. The large numbers of other components in traditional Chinese medicines make the screening and analysis of the bioactive components extremely difficult. By the way, the combination effect of bioactive components on the pharmacological activity makes it very difficult to clear the therapeutic mechanism of TCMs. Therefore, some strategies have to design for screening of bioactive compounds in traditional Chinese medicines, which further leads to disclose the therapeutic mechanism of TCMs in molecular level. The review will summarize the present state of the art of screening strategy for active compounds in traditional Chinese medicines, and the chromatography methods for screening and analysis of bioactive compounds in traditional Chinese medicines will be emphasized. (C) 2004 Elsevier B.V. All rights reserved.

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本论文选择在我国分离得到的一株有毒赤潮甲藻-塔玛亚历山大藻(Alexandrium tamarense,ATHK株),研究了其对一种我国沿海常见和典型养殖鱼类鲈鱼(Lateolabrax japonicus)的危害机制。首先研究了塔玛亚历山大藻(ATHK)对鲈鱼鳃结构的影响及其溶血毒性; 然后采用腹腔注射的方法,研究了高剂量塔玛亚历山大藻毒素(ATHK毒素:约为1.6×105 细胞,相应PSP为0.886µg STX Equal,相当于每克湿重的鲈鱼PSP注射量为0.0118µg STX Equal)和低剂量塔玛亚历山大藻毒素(ATHK毒素: 约为0.16×105 细胞,相应PSP为0.0886µg STX Equal,相当于每克湿重的鲈鱼PSP注射量为0.00118µg STX Equal)在鲈鱼体内代谢过程中对鲈鱼肝脏、肾脏和鳃组织的超微结构、Na+K+-ATPase活性、肝脏功能和肾脏功能的影响、以及对抗氧化系统酶活性和异生物质代谢酶的影响,以期从不同方面了解塔玛亚历山大藻及其所产水溶性毒素(ATHK毒素)对鲈鱼的毒害效应及机制,为有毒赤潮的有效管理提供一定的科学依据。 塔玛亚历山大藻(ATHK)对鲈鱼鳃组织影响的实验结果表明,该藻使鲈鱼鳃组织出现水肿现象,细胞间隙变大;粘液细胞颗粒不规则,颜色加深,颗粒发生凝集,有板结状;氯细胞线粒体内部基质凝集。不产PSP的一种亚历山大藻(AT-6)也使鲈鱼鳃出现水肿,且使细胞出现一定的固缩现象。显微镜观察发现鲈鱼鳃丝间存在有这两种亚历山大藻细胞。由此推测塔玛亚历山大藻ATHK和AT-6的表面结构可能具有能导致鲈鱼鳃组织水肿的机械作用。对人血细胞溶血实验结果表明塔玛亚历山大藻(ATHK)具有较强的溶血毒性,大小与藻的生长阶段和细胞密度都有一定的关系:指数期的溶血毒性最大,随细胞数目的增多,活性逐渐加大;藻细胞、细胞碎片、细胞内容物都有一定的溶血毒性,其中细胞碎片的活性最大。通过11种(株)产PSP的亚历山大藻、不产PSP的亚历山大藻以及标准PSP的实验结果表明这种溶血毒性是由藻细胞的其它非PSP物质造成的,且这种溶血毒性在产PSP的亚历山大藻中具有一定的普遍性。 塔玛亚历山大藻(ATHK)对鲈鱼组织超微结构实验结果表明:ATHK毒素(约为1.6×105 细胞,相应PSP为0.886µg STX Equal,相当于每克湿重的鲈鱼PSP注射量为0.0118µg STX Equal)能导致鲈鱼组织细胞超微结构发生剧烈的变化,主要表现在:肝细胞细胞膜有肿胀现象,部分膜边缘溶解;细胞质糖原颗粒化;核糖体脱落,仅见滑面内质网;细胞质和线粒体内都出现空泡,且线粒体的嵴状结构也发生变化;核膜溶解比较严重,核质外溢,且异染色质边际化。前肾细胞超微结构的变化主要是淋巴细胞核质出现空泡,核膜有溶解迹象;Ⅰ型粒细胞颗粒膨大,伪足增多且变长;Ⅱ型颗粒细胞颗粒增多,内部出现空腔,细胞膜和核膜溶解,胞质、细胞器和核质外溢。鳃组织中氯细胞的核膜局部溶解,核仁弥散,线粒体膜溶解,微细小管膨大;粘液颗粒膜溶解,内部结构遭受破坏;扁平细胞核膜及线粒体膜几乎全部溶解。因此,我们的结果表明,ATHK毒素能作用于鲈鱼细胞的内膜和外膜系统,使膜发生溶解、脱落等变化;比较注射同样剂量大小ATHK毒素120h和240h时鲈鱼组织超微结构发现,细胞超微结构在一定程度上能够恢复。 ATHK毒素对Na+K+-ATPase活性、肝脏功能以及肾脏功能的影响结果表明,0.16×105―1.6×105细胞范围内的ATHK毒素可以显著影响肝脏和鳃组织中的Na+K+-ATPase,使这两种组织中的Na+K+-ATPase活性出现不同程度的下降; 而且还能够显著抑制肝脏中谷丙转氨酶的活性,最大抑制率为95%。但此范围内的ATHK毒素不能显著影响肾脏中的Na+K+-ATPase活性以及尿素氮含量。因此,ATHK毒素对Na+K+-ATPase活性的抑制则会导致细胞能量的缺失,使细胞进一步发生其它变化,而ATHK毒素对肝脏功能完整性的影响则可能会抑制对蛋白质的分解代谢。 ATHK毒素对鲈鱼肝脏、肾脏和鳃组织中的、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱肝肽过氧化物酶(GSH-Px)以及谷胱肝肽转硫酶(GST)活性变化影响的结果表明:高剂量(约为1.6×105 细胞,相应PSP为0.886µg STX Equal,相当于每克湿重的鲈鱼PSP注射量为0.0118µg STX Equal)ATHK毒素能显著诱导鲈鱼肝脏和鳃组织中SOD、GSH-Px以及GST酶活性,最大变化范围为正常状态下的3-4倍,对肝脏中CAT酶活性具有一定的抑制作用,对鳃中的CAT抑制效应则不显著;但此剂量的ATHK毒素仅对肾脏鳃中的GSH-Px活性有一定的诱导作用,对SOD、CAT以及GST的活性没有显著影响。低剂量(约为0.16×105 细胞,相应PSP为0.0886µg STX Equal,相当于每克湿重的鲈鱼PSP注射量为0.00118µg STX Equal)ATHK毒素也能诱导鲈鱼肝脏和鳃组织中SOD、GSH-Px以及GST酶活性,其在第一个24h内的诱导效果与临界致死毒素剂量相似; 且连续注射低剂量ATHK毒素则对肝脏和鳃中这三种酶活性具有累加的诱导作用,使这三种酶活性的变化范围为正常的5倍;低剂量ATHK毒素对肝脏中CAT酶活性也具有抑制作用,但对鳃中CAT酶活性的抑制作用并不显著。 同样,低剂量ATHK毒素除对肾脏中GSH-Px活性具有一定诱导效应外,对SOD、CAT以及GST都没有显著影响。 SOD、GSH-Px以及GST酶活性的显著升高表明ATHK毒素在鲈鱼体内代谢过程中能诱导鲈鱼产生活性氧自由基,且GST活性的升高则说明作为细胞色素P450依赖的异生物质代谢酶,GST在ATHK毒素代谢过程中可能可以加速ATHK毒素的代谢。推测鲈鱼可以通过这三种酶降低ATHK毒素以及次生毒物活性氧自由基对鲈鱼的危害。

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本文研究了腹泻性贝毒的主要组分大田软海绵酸以及几株重要赤潮藻的提取物对四株哺乳类细胞的毒性效应,并探讨了应用细胞毒性检测方法作为赤潮藻毒素毒性检测常规方法的可能性。 结果发现:OA和利玛原甲藻提取物显著地抑制四株细胞的增殖并诱导四株细胞发生凋亡;四株细胞对毒素的敏感性存在一定的差异,人肝癌细胞和小鼠神经瘤细胞较敏感,其次分别为人肝细胞和小鼠皮肤细胞。 小鼠神经瘤细胞对OA反应敏感,细胞毒性检测指标及检测方法灵敏、快速,应用小鼠神经瘤细胞Neuro-2a进行的DSP毒素细胞毒性测试方法具有发展为该类毒素毒性监测常规方法的潜能。 米氏凯伦藻内存在抑制细胞增殖的毒性物质,且该物质是一种具有一定极性的脂溶性物质;该物质能够导致细胞肿胀、破裂,并诱导细胞发生脂质过氧化,导致脂质过氧化产物丙二醛(MDA)的积累。 相关亚历山大藻的去藻过滤液内存在抑制细胞增殖和诱导细胞凋亡的毒性物质,该毒性物质的分子量>5K,这与本实验室以往的研究结果一致。   总之,通过我们的研究发现:DSP等赤潮藻毒素或毒性物质对哺乳类细胞存在毒性影响,且不同毒素的危害机制存在差异,赤潮藻毒素或赤潮藻产生的一些毒性物质威胁人类的健康,应引起我们的高度关注。

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

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The rapid development of nanotechnology has led to a rise in the large-scale production and commercial use of engineered nano-ZnO. Engineered/manufactured nano-ZnO are applied in a broad range of products such as drugs, paints, cosmetics, abrasive agents and insulators. This can result in the unintended exposure of human beings to nano-ZnO and will inevitably result in the release of nano-ZnO in to the environment. Thus, it is necessary to assess the risk of nano-ZnO to the environment. In this thesis the toxicity of nano-ZnO was analysed using the aquatic, primary producer lesser duckweed (Lemna minor), and the mechanism of toxicity was analysed. Both short-term (one week) and long-term (six weeks) toxicity of nano-ZnO (uncoated) were determined. Results show that the toxicity of nano-ZnO added to the aquatic growth medium increases with increasing concentration and that toxicity accumulates with exposure time. A study of nano-ZnO dissolution reveals that the main reason for nano-ZnO toxicity on Lemna minor is the release of Zn ions. Nano-ZnO dissolution is pH dependent, and toxicity matches the release of Zn2+. Functional coating materials are commonly added to nano-ZnO particles to improve specific industrial applications. To test if coating materials contribute to nano-ZnO toxicity on lesser duckweed, the effect of silane coupling agent (KH550) coated nano-ZnO on Lemma minor was investigated. Results show that coating can decrease the release of Zn ions, which reduces toxicity to Lemna minor, in contrast to uncoated particles. Another commonly hypothesized reason for nano-ZnO toxicity is the formation of Reactive Oxygen Species (ROS) on the particles surface. As part of this thesis, the ROS formation induced by nano-ZnO was studied. Results show that nano-ZnO catalyse ROS formation and this can negatively affect duckweed growth. In conclusion, this work has detailed potentially toxic effects of nano-ZnO on Lemna minor. This study has also provides references for future research, and informs regulatory testing for nanoparticle toxicity. Specifically, the outcomes of this study emphasize the importance of exposure time, environmental parameters and coating material when analysing NPs toxicity. Firstly, impacts of longer exposure time should be studied. Secondly, environmental parameters such as pH and medium-composition need to be considered when investigating NPs toxicity. Lastly, coating of NPs should always be considered in the context of NPs toxicity, and similar NPs with different coatings require separate toxicity tests.

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Treatment regimens for solid tumours have been extensively investigated for their physical toxic effects, but far less is known about the potential impairment of cognitive function by anticancer treatment regimens. Here, we review published studies that examined cognitive function in adult patients receiving systemic therapy for solid tumours. Our review suggests that patients can experience cognitive changes related to their treatment. However, several studies had methodological limitations, such as use of a limited sample size, lack of baseline assessment, and lack of control for potential confounding factors. Better designed clinical trials are required so that the difficulties patients face in terms of reduced cognitive function as a result of anticancer treatment can be fully elucidated. These trials should have sufficient statistical power and, importantly, should also be prospective.

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We describe 3 cases of daptomycin-induced pulmonary toxic effects that are consistent with drug-induced acute eosinophilic pneumonia. Patients presented similarly with dyspnea, cough, hypoxia, and diffuse ground-glass opacities at chest computed tomography. Clinical suspicion for this adverse drug event and cessation of daptomycin until definitive diagnosis can be made is crucial.

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Many metals have serious toxic effects when ingested by aquatic organisms, and the process of bioaccumulation intensifies this problem. A better understanding of bioaccumulation trends of anthropogenically introduced metals in freshwater food webs is necessary for the development of effective management strategies to protect aquatic organisms, as well as organisms (including humans) that consume top-predator fish in these food webs. Various fish species representing different trophic levels of a pelagic food chain were sampled from Lake Champlain (VT/NY). Atomic absorption spectrometry (AAS) was used to determine levels of chromium, copper, cobalt, cadmium, lead, zinc, nickel, rubidium, cesium and potassium in the fish samples. Metal concentrations for chromium, cobalt, nickel, cesium, cadmium (<5.0 ppm) and lead (<10.0 ppm) were found to be all below detection limits. Carbon and nitrogen isotopic ratios were analyzed to determine the trophic relationship of each fish species. Stable isotope and AAS metal data were used in tandem to produce linear regressions for each metal against trophic level to assess biomagnification. Both potassium and zinc showed no biomagnification because they are homeostatically regulated essential trace metals. Copper was under the detection limits for all fish species with the exception of the sea lamprey; but showed a significant biodiminution among the invertebrates and lamprey. Rubidium, a rarely studied metal, was shown to increase with trophic level in a marginally significant linear relationship suggesting biomagnification is possible where more trophic levels are sampled.